Udayan Apte, Ph.D.

PhD, University of Louisiana at Monroe, 2003
Postdoctoral Fellowship, University of Pittsburgh, 2008

Research Interests

Pathogenesis of Hepatocellular Carcinoma (HCC), Regulation of Hepatocyte Proliferation during Liver Regeneration

Liver is known for its remarkable capacity to regenerate following surgical resection or in response to drug-induced liver injury. The regenerative capacity of the liver is of immense importance as it affects outcomes of liver toxicity, post-transplant survival and cancer pathogenesis. It is know that following surgical resection of up to 70% liver (partial hepatectomy or PHX), the remnant liver regrows back precisely to the pre-PHX size. Interestingly, many of the pathways involved in normal liver regeneration are oncogenic signaling pathways also involved in cancer pathogenesis. However, these pathways are turned off at precise times during normal liver regeneration, whereas they remain constantly active in cancers. These observations support the existence of specific mechanisms that terminate liver regeneration in a timely fashion and regulate liver size growth following PHX. We are testing the hypothesis that signaling pathways that terminate liver regeneration following PHX are dysfunctional during pathogenesis of hepatocellular carcinoma (HCC), the most common hepatic malignancy. To this end, we are investigating the role of nuclear receptor Hepatocyte Nuclear Factor-4α (HNF4α) in inhibition of hepatocyte proliferation and prevention of HCC pathogenesis.

HCC is the most common hepatic malignancy with extremely grim prognosis and limited treatment options. Incidence of HCC is rising in the US and the world. However, the mechanisms of HCC pathogenesis are not completely known. We are investigating the role of bile acids in HCC pathogenesis. Bile acids are amphipathic molecules produced in the liver and are involved in digestion and absorption of fats and vitamins. Increase in bile acid levels results in hepatic inflammation, cholestatic liver diseases and liver cancer. Higher bile acids are known to promote cancer development in the colon and the liver but the mechanisms are not known. We are investigating the signaling crosstalk between Wnt/ β -catenin pathway and bile acids during HCC pathogenesis.

Recent studies have shown that Hippo Kinase signaling pathway is involved in organ size regulation of the liver and deregulation of this pathway results in HCC development. The downstream effector of this pathway is a protein called yes-associated protein (Yap). Yap is a transcriptional coactivator and is known to stimulate pro-mitogenic signaling. However, recent studies in our laboratory have shown that Yap may also be involved in hepatic differentiation. We are investigating the role of Yap and Hippo Kinase signaling pathway in postnatal hepatic differentiation.

Selected Publications

Apte U, Gkretsi V, Bowen WC, Mars WM, Luo JH, Donhamsetty S, Orr A, Monga SP, Wu WC and Michalopoulos GK. Enhanced liver regeneration following changes induced by hepatocyte-specific genetic ablation of integrin-linked kinase. Hepatology (May 6-Epub ahead of print) 2009.

Apte U, Thompson M, Cui S, Liu B, Zeng G, Cieply B, Monga SP. Wnt/beta-catenin signaling mediates oval cell response in rodents. Hepatology 47:288-95, 2008.

Apte U, Zeng G, Thompson M, Muller P, Micsenyi A, Cieply B, Kaestner KH, Monga SP. Beta-Catenin is critical for early postnatal liver growth. Am J Physiol Gastrointest Liver Physiol 292:G1578-85, 2007.

Zeng G, Apte U, Cieply B, Singh S, Monga SP. siRNA-mediated beta-catenin knockdown in human hepatoma cells results in decreased growth and survival. Neoplasia.9:951-959, 2007.

Apte U M, Zeng G, Muller P, Tan X, Micsenyi A, Cipley B, Dai C, Liu Y, Kaestner KH, Monga SP. Activation of Wnt/beta-Catenin Pathway During Hepatocyte Growth Factor-Induced. Hepatology 44:992-1002, 2006.

Apte UM, Banerjee A, McRee R, Wellberg E, and Ramaiah SK. Role of osteopontin in hepatic neutrophil infiltration during alcoholic steatohepatitis. Toxicol Appl Pharmacol. 207:25-38, 2005.

Corton JC*, Apte U*, Anderson SP, Limaye P, Yoon L, Latendresse J, Dunn C, Everitt JI, Voss KA, Swanson C, Kimbrough C, Wong JS, Gill SS, Chandraratna RA, Kwak MK, Kensler TW, Stulnig TM, Steffensen KR, Gustafsson JA, and Mehendale HM. Mimetics of caloric restriction include agonists of lipid-activated nuclear receptor. J. Biol. Chem. 279:46204-12, 2004. (* Contributed equally to this work)

Apte UM, Limaye PB, Ramaiah SK, Vaidya VS, Bucci TJ, Warbritton A, and Mehendale HM. Upregulated promitogenic signaling via cytokines and growth factors: potential mechanism of robust liver tissue repair in caloric restricted rats upon toxic challenge. Toxicol. Sci. 69:448-459, 2002.

Contact Information

Udayan Apte, Ph.D.
Assistant Professor
Department of Pharmacology, Toxicology and Therapeutics
The University of Kansas Medical Center
4087 HLSIC; MS 1018
3901 Rainbow Blvd.
Kansas City, Kansas 66160
Phone: 913-588-9247
Fax: 913- 588-7501
Email: uapte@kumc.edu

Updated 11/16/10